The invention relates to a non-invasive method for detecting changes in cervical connective tissue using light-induced native fluorescence spectroscopy. More exactly, this invention relates to a procedure useful for determining changes in cervical tissues by recording connective tissue intrinsic fluorescence signals from the cervix of females using light-induced native fluorescence spectroscopy. The extent and progress of such changes relate to maternal readiness for fetal delivery and may be used to diagnose slow progress of labor or other complications.
The cervix is composed almost entirely of connective tissue comprising collagen and macromolecular components which make up the extracellular matrix of this tissue. Many biochemical studies show that there are changes in cervical connective tissue during cervical ripening and dilation during labor. Collagen degradation resulting from increased collagenase activity may be a major element in cervical changes associated with labor. Therefore, an instrument or procedure for instantly and non-invasively measuring these changes would be of great benefit to objectively evaluate the state of the cervix during labor.
Fluorescence spectroscopy is a widely utilized research tool in the biosciences (Udenfriend, 1962), primarily because of the amount of information that it can reveal in terms of molecular physical states (Cantor and Schimmel, 1980). Fluorescent spectra offer important details on the structure and dynamics of macromolecules and their location at microscopic levels (Lakowicz, 1986).
Native fluorescence from intrinsic fluorophors in tissues and cells provides a basis for diagnostic techniques relating to certain diseases (Glassman, 1993). The intrinsic fluorophors, functioning as part of the unique but complicated biological system, change along with the status of cells and tissues. When appropriately applied, tissue fluorescence can provide the medical and veterinary medical fields with a minimally invasive yet highly accurate diagnostic technique. This fluorescence technique has been found to be useful for distinguishing some of the physiological states of abnormal tissues as compared to the corresponding normal tissues (Alfano and Yao, 1981; Alfano et al., 1984; Alfano et al., 1984; Alfano et al., 1987; Alfano et al., 1991). For example, studies have observed differences in the laser or other light-induced native fluorescence spectra between normal tissues and neoplastic tumors in several types of the organs (Tang et al. 1989; Glassman et al. 1991; Cothren et al. 1990; Richards-Kortum et al., 1991; Deckelbaum, et al. 1989; Ma et al., 1990; Glassman et al., 1984). Similar studies have also been done to determine diseased states such as malignancies and dysplasia with human reproductive organs such as cervix, ovary, and uterus (Glassman et al., 1991; Glassman et al., 1994), however this technique has not been applied before to the diagnosis of cervical ripening during pregnancy.
Presently there is no objective manner to evaluate cervical changes associated with dilation and effacement of the cervix during pregnancy. During pregnancy the cervix is normally firm and closed. At the end of pregnancy the cervix becomes softer and dilates as the uterine contractions increase during labor. However, there are many times when the cervix fails to dilate with advancing labor or when the cervix dilates prematurely, prior to labor. The attending physician currently monitors progress of the cervix by visual inspection or by manual examination. However, these subjective tests are often inadequate and vary from physician to physician. An instrument or procedure to more accurately measure cervical changes associated with labor would be invaluable to the diagnosis of cervical problems such as premature dilation or prolonged labor and fetal distress due to delayed cervical dilation.
The present invention provides, for the first time, the ability to accurately and quantitatively determine the status of cervical dilation during pregnancy, and particularly during the last stages of pregnancy and during labor. Differences in the intrinsic fluorescence spectra from the irradiated cervix are observed and compared at various time points during pregnancy and during labor, giving the physician, veterinarian or research scientist instant knowledge of the status of the cervix and cervical opening of an animal or human subject. This knowledge is important for determination of proper treatments. The present invention offers a great improvement over manual palpation and subjective estimation of cervical status as currently practiced. Use of the method described herein will enable safer and more accurate diagnoses concerning the preparation or lack thereof of a prenatal human or animal patient for delivery and recovery.